Effects of adenosine on cardiopulmonary functions and oxygen-derived variables during endotoxemia.
OBJECTIVE
To determine the effects of a prophylactic intravenous infusion of adenosine on cardiopulmonary functions and oxygen-derived variables in a porcine model of endotoxemia.


METHODS
Prospective, randomized, placebo-controlled, unblinded study.


METHODS
University research laboratory.


METHODS
Thirty country bred pigs, aged 6 to 7 wks, weighing 24.9 +/- 0.65 (SEM) kg body weight.


METHODS
Pigs were anesthetized by i.v. pentobarbital and fentanyl, intratracheally intubated, and mechanically normoventilated with a gas mixture of nitrous oxide/oxygen = 1:1. Intravascular catheters were inserted to allow for determination of arterial, central venous blood pressure, pulmonary artery occlusion pressure, cardiac output, and sampling of blood for gas analyses. Group 1 (n = 10) received a 330-min intravenous infusion of Salmonella abortus equi endotoxin (5 microg/kg body weight x hr). Group 2 (n = 10) received an additional intravenous infusion of adenosine (150 microg/kg body weight x min), started 30 mins before the infusion of endotoxin. Control groups 3 and 4 (n = 5 for both groups) received adenosine or physiologic saline, respectively.


RESULTS
Parameters of cardiopulmonary function and oxygen-derived variables were calculated from pulmonary artery catheter measurements and blood gas analyses using standard formula. Plasma concentrations of purine compounds (adenosine, inosine, hypoxanthine) were determined by high-performance liquid chromatography. Since tumor necrosis factor-alpha plays a central role in the development of endotoxic shock, concentrations of this cytokine were determined in serum by enzyme-linked immunosorbent assay. Infusion of adenosine before the beginning of the infusion of endotoxin increased plasma concentrations of the nucleoside from 193 +/- 72 to 553 +/- 65 nmol/L and decreased the systemic vascular resistance by 50%. Although acting as a potent vasodilator under control conditions, adenosine did not aggravate the arterial hypotension elicited by endotoxemia but significantly increased cardiac output by a comparably small decrease in systemic vascular resistance, prevention of pulmonary vasoconstriction, and improvement of left ventricular performance. Despite significant pulmonary vasodilation, gas exchange was not worsened but slightly improved by adenosine. With the increase in cardiac output and arterial oxygenation, systemic oxygen delivery almost doubled. This adenosine-induced oxygen flux was not a surplus but was most likely utilized by tissues, as suggested by the much earlier beginning of the increase in the systemic oxygen consumption and the attenuation of the decrease in the gastric mucosal pHi. No effects of adenosine were observed on the endotoxin-induced increase in serum concentrations of tumor necrosis factor-alpha.


CONCLUSIONS
Infusion of adenosine might be useful to improve flow-dependent oxygen delivery and tissue oxygenation during endotoxic shock without the induction of adverse cardiopulmonary side effects. The beneficial hemodynamic effects of adenosine appear not to be mediated by the inhibition of the release of tumor necrosis factor-alpha.
Thiel
M
M
Institute for Surgical Research, Klinikum Grosshadern, Ludwig-Maximilians-University Munich, Germany.
Kreimeier
U
U
Holzer
K
K
Moritz
S
S
Peter
K
K
Messmer
K
K
D000241:Adenosine / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D019446:Endotoxemia / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D005260:Female; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects; D007262:Infusions, Intravenous; D008168:Lung / Q000187:drug effects* / Q000503:physiopathology; D010100:Oxygen / Q000097:blood*; D011446:Prospective Studies; D011897:Random Allocation; D012481:Salmonella Infections, Animal / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D013552:Swine; D013997:Time Factors; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*
D014665:Vasodilator Agents; D000241:Adenosine; D010100:Oxygen